Submissions for variant NM_007294.4(BRCA1):c.3024G>A (p.Met1008Ile)

gnomAD frequency: 0.00065  dbSNP: rs1800704

Total submissions: 31

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077535	SCV000244331	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2015-08-10	reviewed by expert panel	curation	IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.0000000196
Labcorp Genetics (formerly Invitae), Labcorp	RCV000048051	SCV000076064	benign	Hereditary breast ovarian cancer syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Counsyl	RCV000077535	SCV000154015	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-01-24	criteria provided, single submitter	literature only
Ambry Genetics	RCV000162535	SCV000212936	benign	Hereditary cancer-predisposing syndrome	2014-11-18	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492337	SCV000219225	benign	Breast and/or ovarian cancer	2023-05-05	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000048051	SCV000267854	likely benign	Hereditary breast ovarian cancer syndrome	2016-04-25	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000120291	SCV000333834	likely benign	not specified	2015-08-12	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000120291	SCV000538436	likely benign	not specified	2016-03-29	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.2% (25/11568) Latino; ClinVar: 5 B/LB, 3 VUS
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency	RCV000120291	SCV000586889	benign	not specified	2017-04-18	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162535	SCV000683083	likely benign	Hereditary cancer-predisposing syndrome	2015-02-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000120291	SCV000806927	benign	not specified	2017-01-30	criteria provided, single submitter	clinical testing
Mendelics	RCV000077535	SCV001140564	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000077535	SCV001287309	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-08-14	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034737	SCV001474354	benign	not provided	2022-07-08	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000048051	SCV002025966	benign	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000120291	SCV002065814	benign	not specified	2018-06-22	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162535	SCV002538174	benign	Hereditary cancer-predisposing syndrome	2020-02-24	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV000034737	SCV002585647	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	BRCA1: BP4, BS1, BS2
Fulgent Genetics, Fulgent Genetics	RCV002504869	SCV002806248	likely benign	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 1; Pancreatic cancer, susceptibility to, 4; Fanconi anemia, complementation group S	2021-09-02	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000077535	SCV004016751	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2023-07-07	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000120291	SCV004026781	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000077535	SCV004815616	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000034737	SCV005251062	benign	not provided		criteria provided, single submitter	not provided
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000077535	SCV000043171	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2023-10-06	no assertion criteria provided	research	BS1 based on allele frequency in AJ population of 0.010807 in gnomAD. REVEL score of 0.452. PMID:23867111 showed function like WT.
ITMI	RCV000120291	SCV000084443	not provided	not specified	2013-09-19	no assertion provided	reference population
Sharing Clinical Reports Project (SCRP)	RCV000077535	SCV000109336	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2012-10-23	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077535	SCV000144613	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Pathway Genomics	RCV000077535	SCV000187724	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-07-24	no assertion criteria provided	literature only
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000077535	SCV000591420	benign	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion criteria provided	clinical testing	Also identified by our lab once in an individual with a second pathogenic mutation AJ mutation - JLE
True Health Diagnostics	RCV000162535	SCV000886669	benign	Hereditary cancer-predisposing syndrome	2018-09-28	no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000077535	SCV004244065	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2020-03-02	no assertion criteria provided	clinical testing